BACKGROUND:Cyclophosphamide (CTX)-induced ovarian dysfunction and infertility represent significant concerns for reproductive-age or younger female cancer patients. Although various fertility preservation techniques are currently accessible, there remains a pressing demand for an efficient, non-invasive strategy to protect ovarian function that can be employed concurrently with chemotherapy. Considering the significance of nicotinamide adenine dinucleotide (NAD+) in regulating DNA damage and apoptosis, we aimed to examine the protective effects of nicotinamide mononucleotide (NMN, an NAD+ precursor) on ovarian function against CTX-induced damage. RESULTS:Eight-week-old female C57 mice were underwent to a 14-day treatment protocol, receiving either saline, CTX, or CTX combined with NMN supplementation. The protective effects of NMN supplementation during CTX treatment on ovarian reserve, oocyte quality, and developmental competence were evaluated. NMN supplementation during CTX treatment increased NAD+ content in the ovary, improved ovarian reserve, enhanced endocrine function, reduced reactive oxygen species (ROS) levels, alleviated DNA damage, and reduced apoptosis. Furthermore, this supplementation improved the rates of two-cell embryo and blastocyst formation, increased total cell counts, while decreasing ROS levels, DNA damage, and apoptosis in blastocysts. Moreover, the protective mechanisms of NMN may involve key genes such as Banp and Rbm47 in the ovarian tissue, along with serum/glucocorticoid-regulated kinase 1 (Sgk1) in oocytes. CONCLUSIONS:Collectively, our results highlight the protective effects of NMN against CTX-induced damage to the reproductive function, thus addressing a critical gap in fertility preservation. We present a potential non-invasive strategy that does not interfere with cancer therapy timelines.
In this study, we aimed to investigate the molecular mechanisms of RNA N6-methyladenosine (m6A) modification and how its associated proteins affect granulosa cell aging. A granulosa cell senescence model was constructed to detect the differences in total RNA m6A modification levels and the expression of related enzymes. Changes in downstream molecular expression and the effects on the cellular senescence phenotype were explored by repeatedly knocking down and overexpressing the key genes fat mass and obesity-associated protein (FTO), YT521-B homology domain family member 2 (YTHDF2), and matrix metalloproteinase-2 (MMP2). There was an increased total RNA m6A modification and decreased expression of the demethylase FTO and target gene MMP2 in senescent granulosa cells. FTO and MMP2 knockdown promoted granulosa cell senescence, whereas FTO and MMP2 overexpression retarded it. YTHDF2 and FTO can bind to the messenger RNA of MMP2. The extracellular signal-regulated kinase (ERK) pathway, which is downstream of MMP2, retarded the process of granulosa cell senescence through ERK activators. In granulosa cells, FTO can regulate the expression of MMP2 in an m6A-YTHDF2-dependent manner, influencing the activation status of the ERK pathway and contributing to the aging process of granulosa cells.
BackgroundEndometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery remains unclear.MethodsWe explored the association between the various phenotypes of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women’s menstruation, ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed.ResultsMR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960–0.986) and normal delivery (OR = 0.999, 95% CI: 0.998–1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965–0.988) and normal delivery (OR = 0.999, 95% CI: 0.998–1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942–0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216–0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence.ConclusionOur findings deepen the understanding of the relationship between various types of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis.
BackgroundReproduction-related congenital birth defects (RCBDs), including Klinefelter syndrome (KS), Turner syndrome (TS), and urogenital congenital anomalies (UCA), can lead to severe physical and psychosocial disorders. The global impact of RCBDs on children and adults is unknown, which limits high-quality development of populations and increases in life expectancy per capita.MethodsAnnual incidence rates, prevalence rates (PR), and disability-adjusted life year (DALY) rates were collected for KS, TS, and UCA for 204 countries and territories, including at birth, for children younger than 1 year, and age-standardized (AS) for all ages. Linear regression was used to calculate their estimated annual percentage changes (EAPCs). Finally, the relationships between EAPCs of each indicator and sociodemographic index (SDI) was investigated using Pearson correlation analysis.ResultsGlobally, the age-standardized prevalence rate (ASPR) trend is decreasing in KS and TS and increasing in UCA. The DALY rates for children younger than 1 year were on a downward trend in KS and UCA, while they were still rising for TS. The AS-DALY rates were all on a downward trend in KS, TS, and UCA. The DALY rates of KS, TS and UCA were found higher in high-income countries in North America. In addition, the burdens of TS and UCA went down with increasing SDI, whereas the burden of KS increased with increasing SDI.ConclusionThe global burdens of RCBDs have decreased since 1990. This finding can help policymakers implement cost-effective interventions to reduce the burdens of RCBDs.
Introduction Currently, the treatment strategies for angular pregnancy in the first trimester after assisted reproduction technology (ART) are unclear. Improper treatment will cause unnecessary losses to patients, especially infertile patients, after ART. The purpose of this study was to clarify the pregnancy outcomes of expectant treatment for angular pregnancy post-ART and to provide a basis for the formulation of clinical treatment strategies. Method This retrospective case series study was performed at the Reproductive Medicine Center of a university hospital. Maternal data and pregnancy outcomes were collected and analyzed for all patients diagnosed with angular pregnancies after ART between January 2016 and August 2021. The outcomes included live birth, term birth, premature birth, early pregnancy loss, fetal death, placental abruption, uterine rupture, maternal death, and hysterectomy. Results A total of 78 patients were analyzed in this study, of whom 54 (69.2%) had live births, 44 (56.4%) had term births, 21 (26.9%) had an early pregnancy loss, 1 (1.3%) had mid-trimester missed abortion, 1 (1.3%) underwent mid-trimester labor induction due to fetal malformation, and 1 (1.3%) underwent uterine rupture. There were no cases of maternal death, placental abruption, or hysterectomies. Discussion Angular pregnancy after ART is not as dangerous as that described in previous studies; most cases could be treated expectantly under close-interval follow-up and obtain live birth.
Ovarian tissue oocyte (OTO) in vitro maturation (IVM) is a strategy to improve fertility preservation efficiency. Here, the effects of capacitation IVM (CAPA-IVM) on OTO function were investigated. Immature cumulus-oocyte complexes (COCs) from unstimulated 28-day-old mouse ovaries (mimicking OTOs) underwent CAPA-IVM, standard IVM (S-IVM) or in vivo maturation following ovarian stimulation (OS; positive control), and oocyte meiotic maturation and cytoplasmic quality were assessed. CAPA-IVM resulted in improved oocyte meiotic maturation (P < 0.05) and cumulus expansion (P < 0.0001) compared to S-IVM, with expansion comparable to the OS group. MII OTO ROS was lower after CAPA-IVM than S-IVM (P < 0.0001) but not as low as in the OS group (P = 0.036). CAPA-IVM resulted in a better oocyte mitochondrial distribution than S-IVM (P < 0.05) and was similar to the OS group (P > 0.05). Mitochondrial membrane potential in MII OTOs was higher after CAPA-IVM than S-IVM and OS (P < 0.0001). Compared with S-IVM, CAPA-IVM resulted in lower rates of spindle/chromosome configuration and cortical granule distribution abnormalities (P < 0.05), which were similar to OS levels (P > 0.05). MII OTO intracellular Ca2+ levels were similar in the CAPA-IVM and OS groups (P > 0.05), while S-IVM decreased intracellular Ca2+ (P < 0.05). CAPA-IVM and S-IVM decreased mitochondrial Ca2+ levels (P < 0.05). CAPA-IVM increased expression of antioxidant genes (Sod2 and Sirt1) and Egfr (P < 0.05) but not apoptotic genes (Bcl2, Bax and Bcl2/Bax; P > 0.05). CAPA-IVM increased the OTO maturation rate and quality of oocytes from unstimulated mice to the extent that many features of oocyte cytoplasmic quality were comparable to superovulated in vivo matured oocytes.
Some concern has been expressed regarding the negative effects of low-level ionizing radiation exposure in the context of radiological evaluation prior to IVF/ICSI treatment, but the available evidence is limited and conflicting. The aim of this study is to evaluate pregnancy and neonatal outcomes of couples who did chest computed tomography (CT) prior to IVF/ICSI. This was a retrospective cohort study of 2680 IVF/ICSI fresh embryo transfer cycles conducted from January 2019 – August 2020. Fertility outcomes were compared between couples that had or had not undergone CT examination within 3 months prior to the date of oocyte retrieval and sperm collection. Miscarriage was the primary study outcome, while secondary outcomes included the number of oocytes collected, oocyte maturation, normal fertilization, number of good quality cleavage stage embryos, blastocyst formation, implantation, clinical pregnancy, ectopic pregnancy, live birth, multiple birth, Cesarean section rates, gestational weeks, maternal obstetric complications, birth weight, newborn sex ratio, and birth defect incidence. Propensity score matching was used to control for potential confounding variables. Of the 2680 cycles included in this study, couples underwent CT examination in 731 cycles. After 1:1 propensity score matching, 670 cycles were included in each group. When comparing demographic and fertility-related variables between groups that had and had not undergone CT examination after propensity score matching, we detected no significant differences in miscarriage rates (16.99
Background The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (m 6 A) methylation regulate mRNA fate and translational efficiency. However, whether m 6 A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m 6 A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group). Results m 6 A methylation distribution was highly conserved and enriched in the CDS and 3’UTR region. Besides, an increased number of m 6 A methylated genes were identified in the older group. Bioinformatics analysis indicated that m 6 A methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by m 6 A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m 6 A, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary. Conclusions Hence, our finding revealed the transcriptional significance of m 6 A modifications and provide potential therapeutic targets to promote fertility reservation for aging women.
This study evaluated the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. A total of 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles from 2014 to 2020 were divided into normal (18.5–24.9 kg/m 2 ) and high BMI (≥ 25 kg/m 2 ) groups. Ovarian response, pregnancy outcomes, and safety of both mother and fetus were the main outcome measures. Furthermore, multivariate analysis was used to determine whether BMI was associated with cumulative live birth rate (CLBR). Results showed that for younger women (< 38 year), CLBR was significantly reduced in the high BMI group compared with the normal BMI control and was accompanied by fewer retrieved oocytes and available embryos. Additionally, the incidence of hypertensive disorders of pregnancy, fetal macrosomia, and cleft lip and palate birth defects resulting from cumulative live births was significantly higher compared with the normal BMI group. No differences were observed among older women (≥ 38 year). Multivariate analysis revealed that high BMI was a risk factor for CLBR. Our study suggested that elevated BMI has a greater adverse impact on younger women.
PURPOSE:To report a case of successful ovarian stimulation and pregnancy in an infertile woman with Rathke's cleft cyst (RCC). METHODS:This is a case report of a 32-year-old infertile woman with RCC presenting with secondary amenorrhea and hypogonadotropic hypogonadism (HH). Three rounds of ovarian stimulation and ovulation induction by means of HMG and HCG were performed (two before HSG and one after HSG). HSG was performed after two rounds of ovulation induction without pregnancy to assess the fallopian tubes and uterine cavity of the patient. Serum beta-human chorionic gonadotropin (β-HCG) and ultrasound examination were performed after the third round of ovulation induction to confirm successful pregnancy. RESULTS:HSG revealed that the uterine cavity was normal and that the bilateral fallopian tubes were unobstructed. Four weeks after the third round of ovulation induction, the β-HCG test was positive (10261 μg/L), and ultrasound examination showed an intrauterine early gestational sac with an embryo (10*7 mm) and a primitive heart tube pulse. CONCLUSIONS:Infertility accompanied by RCC is rare in the clinic. Clarifying the cause of infertility and secondary amenorrhea is very important for achieving a successful pregnancy. This case demonstrates that such infertility can be treated effectively with ovarian stimulation and ovulation induction using HMG and HCG. To the best of our knowledge, this is the first case report of infertility accompanied by RCC.
Objective: To evaluate the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. Design: Retrospective cohort study. Setting: Teaching hospital. Population: Overall, 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles during 2014-2020. Methods: The patients were divided into normal (18.5–24.9 kg/m2) and high BMI (≥ 25 kg/m2) groups. Subgroup analyses were performed based on the boundary of 38 years old. Multivariate analysis was used to determine whether BMI was associated with live birth rate (LBR) or cumulative live birth rate (CLBR). Main Outcome Measure: Ovarian response, pregnancy outcomes, and safety for both mother and fetus. Results: For younger women (< 38y), CLBR was significantly reduced in the high BMI subgroup compared to the normal BMI control (73.7% vs 76.8%, p = 0.008) and was accompanied by fewer retrieved oocytes and available embryos. Meanwhile, the incidences of cesarean section (92.9% vs 87.1%, p < 0.001), hypertensive disorders of pregnancy (6.7% vs 3.1%, p < 0.001), fetal macrosomia (4.7% vs 2.8%, p = 0.002) and birth defects involving cleft lip and palate (0.4% vs 0.1%, p = 0.030) were significantly higher than the normal BMI group. However, no such differences were observed among older women (≥ 38y). Multivariate analysis revealed that high BMI was a risk factor for CLBR (OR = 0.837, 95% CI: 0.729–0.96). Conclusions: Elevated BMI has a greater adverse impact on younger women.
Reproductive aging in female mammals is an irreversible process associated with declining oocyte quality, which is the rate-limiting factor to fertility. Here, we show that this loss of oocyte quality with age accompanies declining levels of the prominent metabolic cofactor nicotinamide adenine dinucleotide (NAD(+)). Treatment with the NAD(+) metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality in aged animals, leading to restoration in fertility, and this can be recapitulated by transgenic overexpression of the NAD(+)-dependent deacylase SIRT2, though deletion of this enzyme does not impair oocyte quality. These benefits of NMN extend to the developing embryo, where supplementation reverses the adverse effect of maternal age on developmental milestones. These findings suggest that late-life restoration of NAD(+) levels represents an opportunity to rescue female reproductive function in mammals.
At present, an improvement in the survival rates of cancer patients and the recent advancements in assisted reproductive technologies have led to remarkable progress in fertility preservation treatments. The methods of fertility protection and preservation for female cancer patients include: gonadotropin releasing hormone analogue (GnRH-a) injection, embryos cryopreservation, mature oocytes cryopreservation, ovarian tissue cryopreservation and implantation, oocytes in vitro maturation, follicles in vitro maturation and artificial ovaries, et al. These methods enable female cancer patients to have children after anti-cancer treatment, improve their quality of life and preserve their hope of becoming mothers. Key words: Fertility preservation; Premature ovarian failure; Embryos cryopreservation; In vitro maturation; Ovarian tissue cryopreservation
Oocyte in vitro maturation (IVM) is a patient-friendly reproductive technology but lower success rates than IVF have limited its uptake. Capacitation-IVM (CAPA-IVM) is an innovative new IVM system currently undergoing clinical evaluation. This study aimed to determine temporal effects of the pre-IVM phase of CAPA-IVM on cumulus function and oocyte developmental competence in mildly-stimulated mice. Immature cumulus oocyte complexes (COCs) derived from mildly stimulated (23 h PMSG) 28-day-old mice underwent pre-IVM for 0–24 h in medium containing c-type natriuretic peptide (CNP), E2, FSH and insulin, prior to IVM (CAPA-IVM). The effect of pre-IVM duration on cumulus cell function and embryo development post-CAPA-IVM/IVF was assessed. Day 6 blastocyst rate increased incrementally with increasing pre-IVM duration: 40.6 ± 2.0%, 45.8 ± 1.2%, 52.2 ± 3.5%, 53.3 ± 5.9%, and 59.9 ± 2.5% for 0, 2, 6, 12, and 24 h pre-IVM, respectively (P < 0.01). DNA content/COC, a measure of cumulus cell proliferation, was significantly higher with 24 h pre-IVM group compared to 0, 2, or 6 h pre-IVM (P < 0.001). Pre-IVM for 24 h significantly increased cumulus expansion and mRNA expression of matrix genes Has2 and Tnfaip6 and Areg relative to no pre-IVM control (P < 0.01). Cumulus-oocyte gap-junctional communication (GJC) was maintained throughout 24 h pre-IVM (P < 0.0001), and GJC loss was slowed during the subsequent IVM phase, whilst meiotic resumption was accelerated (P < 0.05). Pre-IVM increased COC ATP and ADP content (P < 0.05), but not AMP, ATP/ADP, and energy charge. The pre-IVM phase of CAPA-IVM improves the quality of IVM oocytes in a temporally dependent manner and significantly influences cumulus cell function including increased cell proliferation, cumulus expansion, and prolonged cumulus-oocyte GJC.
Objective: We sought to assess the use of surgical treatment, the effect of postoperative adjuvant therapy, and the prognostic factors for survival of patients with primary spinal peripheral primitive neuroectodermal tumors (pPNETs). Patients and Methods: The clinical data of 24 patients, who had been surgically treated from April 2003 to February 2018 and in whom immunohistochemical staining results had confirmed the diagnosis of primary spinal pPNETs, were retrospectively analyzed. To analyze the factors related to prognosis, the Kaplan-Meier method was used for univariate analysis, the log-rank method was used to test the significance of difference, and multivariate analysis was performed using Cox regression. Results: The overall 1-year, 2-year, and 5-year survival rates were 73.2%, 48.1%, and 12.0%, respectively. The median survival time (MST) of all patients was 21 months. Univariate analysis showed that the extent of tumor resection, adjuvant radiotherapy, and chemotherapy were the factors influencing patient prognosis after surgery (all P < 0.05); sex, age, tumor location, and preoperative Karnofsky performance scale (KPS) scores were not the influential factors for prognosis of patients after surgery (all P > 0.05). Multivariate analysis showed that gross total resection (GTR) of tumors and adjuvant radiotherapy were independent factors influencing the prognosis of patients with pPNETs (all P < 0.05). Conclusions: Primary spinal pPNETs are extremely rare, and they have a poor prognosis. Microsurgical GTR of the tumor is the preferred method of treatment. Radiotherapy plays an important role in improving the prognosis of patients with pPNETs. GTR combined with radiotherapy and chemotherapy may be the best treatment modality.
The definition of oocytes in vitro maturation (IVM) is that the maturation in vitro of immature cumulus-oocyte complexs (COCs) collected from antral follicles. IVM was firstly used in human in 1991, but it developed very slowly. Now researchers pay more and more attention to IVM. C-type natriuretic peptide (CNP) can sustain the arrest of oocytes at germinal vesicle (GV) stage. According to this, biphasic IVM system based on CNP is established, and it works effectively in multi-species. Recently, it was proved that this kind of IVM system can improve human oocytes maturation rate and the developmental competence of mature oocytes. This article summarizes the action principle of CNP and the research advances of biphasic IVM system. Key words: In vitro maturation (IVM); C-type natriuretic peptide (CNP); Natriuretic peptide receptor B (NPRB or NPR2)
Label-retaining cells, which are characterized by dormancy or slow cycling, may be identified in a number of human normal and cancer tissues, and these cells demonstrate stem cell potential. In glioblastoma, label-retaining assays to enrich glioma stem cells remain to be fully investigated. In the present study, glioblastoma sphere cells cultured in serum-free medium were initially stained with the cell membrane fluorescent marker DiI. The fluorescence intensity during cell proliferation and sphere reformation was observed. At 2 weeks, the DiI-retaining cells were screened by fluorescence-activated cell sorting and compared phenotypically with the DiI-negative cells in terms of in vitro proliferation, clonogenicity and multipotency and for in vivo tumorigenicity, as well as sensitivity to irradiation and temozolomide treatment. It was observed that DiI-retaining cells accounted for a small proportion, <10%, within the glioblastoma spheres and that DiI-retaining cells proliferated significantly more slowly compared with DiI-negative cells (P=0.011, P=0.035 and P=0.023 in the of NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines). Significantly increased clonogenicity (P=0.002, P=0.034 and P=0.016 in the NCH441, NCH644 and NCH421k glioblastoma sphere cell lines) and three-lineage multipotency were observed in DiI-retaining cells in vitro compared with DiI-negative cells. As few as 100 DiI-retaining cells were able to effectively generate tumors in the immunocompromised mouse brain, whereas the same number of DiI-negative cells possessed no such ability, indicating the increased tumorigenicity of DiI-retaining cells compared with DiI-negative cells. Furthermore, DiI-retaining cells demonstrated significant resistance following irradiation (P=0.012, P=0.024 and P=0.036) and temozolomide (P=0.003, P=0.005 and P=0.029) compared with DiI-negative cells in the NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines, respectively. It was concluded that label-retaining cells in glioblastoma spheres manifest clear stem cell features and that the label-retaining assay may be utilized to further enrich glioma stem cells cultured under serum-free conditions for additional study.
A 55-year-old woman presented with headache, dizziness, and decreased visual acuity. Magnetic resonance imaging revealed a sellar mass with sphenoid sinus extension. The result of hormone showed an obviously high prolactin (815 ng/mL). The mass was resected and diagnosed with aspergillosis pathologically. Postoperatively, the level of prolactin dramatically decreased, and the patient received medical treatment with voriconazole and caspofungin. During a 6-month follow-up, the patient's headache and dizziness disappeared, and visual acuity improved. Therefore, aspergillus sellar abscess could result in hyperprolactinemia and should be considered in the differential diagnosis of a sellar mass, even in immunocompetent patients. A combination of surgery and antifungal therapy could reduce the hyperprolactinemia and improve symptoms.
To investigate the possible relationship between single nucleotide polymorphisms (SNPs) in the anti-Müllerian hormone (AMH) signaling pathway and the incidence of early OHSS, the genomic DNA was isolated from peripheral blood leukocytes of 122 participants (62 patients with early OHSS and 60 patients without OHSS who underwent IVF/ICSI), and SNPs of the AMH and AMHR2 exons were detected directly. Further more, genotype distribution and allele frequency were analyzed. We found seven types of SNPs in the AMH exons, and two of them were missense mutations (rs10407022 and rs182295886). However, these two missense mutations did not increase the risk of early OHSS (rs10407022, P=0.307, OR=1.552, CI 0.668, 3.608; rs182295886, P=0.442, OR=0.359, CI 0.026, 4.883). While it was observed that participants with the SNP (rs10407022) had a relatively higher ovarian response than those without the SNP. Further more, we did not find any SNPs in exons of AMHR2. In conclusion, we analyzed the pathogenesis of OHSS by first investigating the SNPs in the AMH signaling pathway. There is no association between SNPs in the AMH/AMHR2 signaling pathway and early OHSS in Han Chinese women.